hypersensitive chapter 16 Reactions N IMMUNE RESPONSE MOBILIZES A BATTERY OF effector molecules that act to remove antigen by various mechanisms described in previous chap ters. Generally, these effector molecules induce a localized inflammatory response that eliminates antigen without extensively damaging the host's tissue. Under certain cir- cumstances, however, this inflammatory response can have deleterious effects, resulting in significant tissue damage or even death. This inappropriate immune response is termed hypersensitivity or allergy. Although the word hypersens A Second Exposure to Poison Oak May Result in Delayed-Type Hypersensitivity ivity implies an increased response, the response is not always heightened but may, instead, be an inappropriate im mune response to an antigen. Hypersensitive reactions may Gell and Coombs Classification develop in the course of either humoral or cell-mediated e IgE-Mediated (Type D) Hypersensitivity responses The ability of the immune system to respond inappro- a Antibody-Mediated Cytotoxic (Type Il) priately to antigenic challenge was recognized early in this Hypersensitivity century. Two French scientists, Paul Portier and Charles a Immune Complex-Mediated (Type lID Richet, investigated the problem of bathers in the Mediter- Hypersensitivity ranean reacting violently to the stings of Portuguese Man of Warjellyfish. Portier and Richet concluded that the localized Type IV or Delayed-Type Hypersensitivity(DTH) reaction of the bathers was the result of toxins To counteract this reaction, the scientists experimented with the use of isolated jellyfish toxins as vaccines. Their first attempts met with disastrous results. Portier and Richet injected dogs with the purified toxins, followed later by a booster of toxins Instead of reacting to the booster by producing antibodies against the toxins, the dogs immediately reacted with vomit- ing, diarrhea, asphyxia, and, in some instances, death. Clear- Gell and Coombs Classification the antigen Portier and Richet coined the term anaphylaxis, Several forms of hypersensitive reaction can be distin- loosely translated from Greek to mean the opposite of guished, reflecting differences in the effector molecules gen- prophylaxis, to describe this overreaction. Richet was subse- erated in the course of the reaction In immediate hypersen- quently awarded the Nobel Prize in Physiology or Medicine sitive reactions, different antibody isotypes induce different in 1913 for his work on anaphylaxis immune effector molecules. IgE antibodies, for example, bu We currently refer to anaphylactic reactions within the induce mast-cell degranulation with release of histamine Imoral branch initiated by antibody or antigen-antibody and other biologically active molecules. IgG and IgM anti- complexes as immediate hypersensitivity, because the symp- bodies, on the other hand, induce hypersensitive reactions toms are manifest within minutes or hours after a sensitized by activating complement. The effector molecules in the recipient encounters antigen. Delayed-type hypersensitiv- complement reactions are the membrane-attack complex ity (dTh) is so named in recognition of the delay of symp- and such complement split products as C3a, C4a, and C5a toms until days after exposure. This chapter examines t In delayed-type hypersensitivity reactions, the effector mechanisms and consequences of the four primary types of molecules are various cytokines secreted by activated TH hypersensitive reactions. Tc cells■ Gell and Coombs Classification ■ IgE-Mediated (Type I) Hypersensitivity ■ Antibody-Mediated Cytotoxic (Type II) Hypersensitivity ■ Immune Complex–Mediated (Type III) Hypersensitivity ■ Type IV or Delayed-Type Hypersensitivity (DTH) A Second Exposure to Poison Oak May Result in Delayed-Type Hypersensitivity Hypersensitive Reactions A       effector molecules that act to remove antigen by various mechanisms described in previous chap￾ters. Generally, these effector molecules induce a localized inflammatory response that eliminates antigen without extensively damaging the host’s tissue. Under certain cir￾cumstances, however, this inflammatory response can have deleterious effects, resulting in significant tissue damage or even death. This inappropriate immune response is termed hypersensitivity or allergy. Although the word hypersensi￾tivity implies an increased response, the response is not always heightened but may, instead, be an inappropriate im￾mune response to an antigen. Hypersensitive reactions may develop in the course of either humoral or cell-mediated responses. The ability of the immune system to respond inappro￾priately to antigenic challenge was recognized early in this century. Two French scientists, Paul Portier and Charles Richet, investigated the problem of bathers in the Mediter￾ranean reacting violently to the stings of Portuguese Man of War jellyfish. Portier and Richet concluded that the localized reaction of the bathers was the result of toxins. To counteract this reaction, the scientists experimented with the use of isolated jellyfish toxins as vaccines. Their first attempts met with disastrous results. Portier and Richet injected dogs with the purified toxins, followed later by a booster of toxins. Instead of reacting to the booster by producing antibodies against the toxins, the dogs immediately reacted with vomit￾ing, diarrhea, asphyxia, and, in some instances, death. Clear￾ly this was an instance where the animals “overreacted” to the antigen. Portier and Richet coined the term anaphylaxis, loosely translated from Greek to mean the opposite of prophylaxis, to describe this overreaction. Richet was subse￾quently awarded the Nobel Prize in Physiology or Medicine in 1913 for his work on anaphylaxis. We currently refer to anaphylactic reactions within the humoral branch initiated by antibody or antigen-antibody complexes as immediate hypersensitivity, because the symp￾toms are manifest within minutes or hours after a sensitized recipient encounters antigen. Delayed-type hypersensitiv￾ity (DTH) is so named in recognition of the delay of symp￾toms until days after exposure. This chapter examines the mechanisms and consequences of the four primary types of hypersensitive reactions. Gell and Coombs Classification Several forms of hypersensitive reaction can be distin￾guished, reflecting differences in the effector molecules gen￾erated in the course of the reaction. In immediate hypersen￾sitive reactions, different antibody isotypes induce different immune effector molecules. IgE antibodies, for example, induce mast-cell degranulation with release of histamine and other biologically active molecules. IgG and IgM anti￾bodies, on the other hand, induce hypersensitive reactions by activating complement. The effector molecules in the complement reactions are the membrane-attack complex and such complement split products as C3a, C4a, and C5a. In delayed-type hypersensitivity reactions, the effector molecules are various cytokines secreted by activated TH or TC cells. chapter 16